The major objective of our research project is to improve understanding of the pathogenesis of anaphylaxis by examining for the means by which the kallikrein-kinin system contributes to acute lung dysfunction. We have found that lungs contain two kallikrein-like enzymes and a store of kininogen independent of the plasma kallikrein-kinin system. To clarify possible means of intrapulmonary kinin formation, we propose to purify and characterize the lung kallikreins and kininogen. The specificity of the kallikreins will be examined by determining the kinds of kinins formed. In addition, we will investigate the cellular sites of the kallikreins using isolated cells and intact lungs. The latter studies will require cytochemical and immunocytochemical techniques at the level of electron microscopy, and the former study will require cell culture. Further to define intrapulmonary actions of the kallikrein-kinin system, we will examine for interactions of kinins with specific cell-types of lungs in terms of the synthesis of prostaglandin-related substances. Normal, sensitized and anaphylactic lung tissue will be used throughout. By proceeding along these lines, it should be possible to help detail molecular and cellular mechanisms by which kinins are formed and exert their actions in pulmonary anaphylaxis. The data should provide clues for the development of modification reactions of therapeutic benefit.